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  • 1
    Online Resource
    Online Resource
    International Union of Crystallography (IUCr) ; 2018
    In:  IUCrJ Vol. 5, No. 4 ( 2018-07-01), p. 375-381
    In: IUCrJ, International Union of Crystallography (IUCr), Vol. 5, No. 4 ( 2018-07-01), p. 375-381
    Abstract: Cryo-electron microscopy (cryo-EM) directly images the distribution of electrostatic potential (ESP) within macromolecules, and thus can provide much more information about atomic charge than X-ray crystallography. The electron-scattering length of an isolated ion is quite different from that of the corresponding neutral atom. The difference is very large at small scattering angles where the effects of electron distributions are largest, but becomes smaller at high scattering angles where nuclear charge determines outcomes. For this reason, in cryo-EM maps that have been solved at resolutions lower than ∼2.5 Å, peaks corresponding to anions will always be less prominent than those of cations, and may even be negative. Furthermore, if a map of this kind is smeared computationally after the fact, which reduces its effective resolution, anion peaks will diminish in size, cation peaks will grow and peaks that represent uncharged atoms will remain about the same. These effects can be used to determine the sign of the charges carried by the ions associated with a macromolecule and even estimate their magnitudes. The ESP value for a cation in a cation–anion pair is smaller than the value of the cation in isolation, but the ESP value for the anion in the ionic pair is greater than the value of the anion in isolation. The experimental range of ESP values for Mg 2+ relative to that of the closest C1′ atom is found to be between 0.57 and 1.27.
    Type of Medium: Online Resource
    ISSN: 2052-2525
    Language: Unknown
    Publisher: International Union of Crystallography (IUCr)
    Publication Date: 2018
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  • 2
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 5441-5441
    Abstract: Objective: To investigate and analyze factors which effect autologous stem cell collection in patients with lymphoma and multiple myeloma (MM) during chemotherapy combined with G-CSF mobilization, for improving quality and effectiveness of autologous stem cell transplantation. Methods: A retrospective analysis was performed from April 1, 2006 to October 31, 2013 in our hospital and 128 lymphoma and MM patients whose autologous peripheral blood stem cells (PBSCs) were collected including 75 patients with malignant lymphoma,7 cases of Hodgkin's lymphoma and 68 non-Hodgkin's lymphoma (NHL) cases as well as 53 MM patients were enrolled. The stem cells of all patients were mobilized by chemotherapy combined with G-CSF and collected via a continuous flow cell separation instrument (COBE Spectra, Lakewood, CO). Mobilize failure was defined when the amount of CD34 + cells was less than 2.0 x 106 / kg, whereas ≥2.0 * 106 / kg was defined as successful mobilization. More than 5.0x 106 cells / kg or more was considrered as ideal mobilization. Univariate and multivariate regression analyses of factors for mobilization failure, successful mobilization and ideal mobilization acquisition were performed. Results: There were more CD34+ cells in MM patients than in lymphoma patients (P = 0.064). The collection rates of CD34 + cells in MM patients were ≥ 2.0 x106 / kg in 64.8% (83 cases) and ≥ 5.0 x 106 / kg in 35.2% (45 cases). MM patients with a success collection ratio was 73.6 % (39/53) and the ideal collection rate was 43.4% (23/53), which was higher than in the NHL group with a success rate and ideal rate of 58.7% (44/75) and 30.7% (23/75). A total of 35.2 % (45 cases, including 31MM cases and 14 lymphoma cases) a mobilization was not successful. Conclusion: In different chemotherapy regimens in patients with lymphoma, remission, ever use MTX and/or Ara-c treatment and collecting the outer peripheral hematocrit could significantly affect the success rate of stem cell collection; In MM patients, who received lenalidomide treatment and multiple courses of treatment, still not got CR, which these reasons were the factors of non- successful mobilization.Although Plerixafor and peripheral blood CD34-positive cell counts could help to improve the success collection rate and predict collection rate, but there is still a need for further improvement of the current mobilization protocols, recognizing the ideal stem cell collection dynamics, efficiency and cost in order to select the appropriate mobilization protocols. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
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  • 3
    In: OncoImmunology, Informa UK Limited, Vol. 6, No. 3 ( 2017-03-04), p. e1277307-
    Type of Medium: Online Resource
    ISSN: 2162-402X
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2017
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  • 4
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 2461-2461
    Abstract: Objective: Iron overload is common in patients with acute leukemia who undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT). We performed a comprehensive analysis of iron parameters to assess these patients' iron metabolism, and studied the prognostic impact of pretransplant iron overload on the outcome of transplantation. Methods: In this retrospective study, we studied 124 patients undergoing myeloablative allo-HSCT between 2012 and 2014. Serum iron (SI), serum ferritin (SF), hepcidin (Hepc) and soluble transferrin receptor (sTfR) were measured before transplant. We analyzed the effect of elevated pretransplant ferritin on acute graft versus host disease (aGVHD), infectious complications, overall survival (OS) and non-relapse mortality (NRM). Results: Date of 124 patients (including 56 cases of acute lymphocytic leukemia and 68 cases of acute myeloid leukemia) were analyzed. Median SI, SF, Hepc and sTfR values were 12.15 umol/L, 667.05 ng/ml, 369.50 ng/L and 7.69 ng/ml, respectively. Iron overload (defined as SF 〉 1000 ng/ml) were observed in 27.42% of patients. Pretransplant iron overload was significantly associated with increased risk of bacterial infections during the early post-transplant period, and with reduced risk of aGVHD. Pretransplant iron overload increased NRM and reduced OS, but there were no significant differences. Conclusion: Patients with acute leukemia regularly develop iron overload before they undergoing allo-HSCT. Pretransplant iron overload was correlated with transplantation outcome. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
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  • 5
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 4511-4511
    Abstract: Abstract 4511 Background: Hematologic relapse after Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) is associated with a dismal prognosis. Increasing minimal residual disease (MRD) after HSCT had been proved highly effective prognostic factor for post-treatment leukemia relapse. Savage chemotherapy or intensive conditioning followed by a second HSCT may be applied, but associated with a high mortality and a low rate of complete remission. Donor lymphocyte infusion (DLI) has been shown to exert a graft-versus-leukemia (GVL) effect and has been successfully used in patients who relapsed after HSCT. Objective: In this retrospective study, we sought to gain insights of the effect of DLI on clinical outcomes such as graft versus host disease (GVHD), overall survival (OS), disease free survival (DFS), and treatment-related mortality (TRM) in patients with either relapsed hematological malignancies or increasing MRD who underwent HSCT. Methods: DLIs were administered to 25 patients [10(40%) acute myeloid leukemia, 10 (40%) acute lymphoblastic leukemia, 5 (20%) chronic myeloid leukemia]. Patients with Acute leukemia had been treated with myeloablative conditioning (BuCy). Patients with chronic myeloid leukemia had been treated with non-myeloablative conditioning(Flu,ATG and Bu). Infusion of al logeneic hematopoietic stem cells are performed at our institution from 2005 to 2010. GVHD prophylaxis consisted of CsA, MMF and MTX.10 patients were diagnosed of hematologic relapse a median of 259 (30–850) days after HSCT. 15 patients had persistent increasing MRD(monitoring with flow cytometry or RT-PCR for Fusion Gene) after HSCT. DLIs were given to patients who had relapsed hematological malignancies or persistent increasing MRD. Patients with relapsed malignancies were performed reinduction chemotherapy simultaneously. A total of 57 DLIs were administered to 25 patients a median of 809 (92-1981) days after HSCT. The median transplant dose of CD3(+) cells is 4.12*10e7/kg (2.68*10e7/kg–7.97*10e7/kg). Results: The overall response rate of DLI was 80% for CML, 90% for ALL and 80% for AML.The response rate was 93.3% in patients with increasing MRD, whereas 60% in patients with relapsed malignancies. A total of 10 patients (40%,7 with increasing MRD, 3 with relapsed malignancies) developed acute GVHD. A complete response was achieved in 72% of the patients. TRM was 12% (3 patients with increasing MRD). The Kaplan-Meier estimate of OS and DFS at 3 years after DLI were 62.5% and 60.9%, respectively, with a median follow-up of 411 (32-1509) days for survivors. In patients with increasing MRD, the 3-year OS and DFS after DLI were 78.6% and 77.8%, respectively, with a median follow-up of 531(40-1509) days. In patients with relapsed malignancies,the 3-year OS and DFS after DLI were 40% and 36.8%, respectively, with a median follow-up of 469 (32-1393) days. Conclusion: Leukemia relapse is a serious therapeutic challenge following HSCT. In this retrospective study, DLIs was proved to be an effectively therapy to prevent relapse and get a better Clinical outcome in leukemia patients. Patients undergone DLI without leukemia relapse had a better outcome than the relapse group. Further strategies are required to detect early relapse in HSCT patients, and DLI may be a strategy to prevent relapse in high risk patients. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
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  • 6
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 5075-5075
    Abstract: Abstract 5075 Multiple myeloma (MM) is a malignant disorder characterized by abnormal proliferation of monoclonal, immunoglobulin producing plasma cells in the bone marrow. Studies with large samples have shown that molecular cytogenetic changes play an important role in the prognosis of MM. Based upon these findings, we tested cytogenetic aberrations of 65 patients with MM by conventional cytogenetics analysis and FISH technique in this study. Retrospective study was done on these cases for clinical features. Methods: This is a retrospective analysis of 65 patients with MM diagnosed between June 2007 and May 2010 including 13 relapsed cases and 52 newly diagnosed patients. Patients received bortezomib-based combination chemotherapy including bortezomib plus dexamethasone (BD) and the triplet combinations (bortezomib, adriamycin, dexamethasone (BAD), bortezomib, cytoxan, dexamethasone (BCD) and bortezomib, melphalan, prednisone (BMP) or traditional chemotherapy including doxorubicin, vincristine plus dexamethasone (VAD), melphalan plus dexamethasone (MP), melphalan, dexamethasone plus thalidomide (MPT)). To further clarify the correlation between cytogenetic and clinical features on patients with multiple myeloma, we used conventional cytogenetics analysis with R-banding technique and interphase fluorescence in situ hybridization (FISH) to describe the molecular cytogenetic characterization of bone marrow nucleated cells from 65 patients. SPSS (version 18.0) software was used for data analysis, χ2 tests or Fisher's exact test was used for betweengroup comparison of the discrete variables and Log- Rank was used for survival analysis. p 〈 0.05 reflects the remarkable significance. Results: 16.9% of patients (11/65) showed abnormal cytogenetic aberrations including 90.9% (10/11) cases with ultra complex aberration and complex aberration via conventional cytogenetics. In addition, we were able to show aberrations in 49.2% (32/65) of patients by interphase FISH analysis. Abnormalities of 13q14, 1q21, 14q32 and 17p13 were detected in 27.7% (18/65), 13.8% (9/65), 16.9% (11/65), and 29.2% (19/65) by FISH, respectively. 1q21 amplification is strongly associated with 13q14 mutation (P=0.008), demonstrating significant correlation between two. Abnormality of 13q14 deletion or 1q21 amplification were associated with lower levels of albumin (P 〈 0.05). Patients with 13q14 deletion frequently had stage III disease by DS and ISS staging, and compared with patients not detected on FISH analysis, they tended to have elevated serum levels of β2-microglobulin at diagnosis (P 〈 0.05). 17p13 deletion coexistent with 13q14 deletion frequently correlate with elevated serum levels of β2-microglobulin and advanced clinical staging. The median progression-free survival (PFS) of patients with 17p13 deletion or 17p13/13q14 aberrations were both 11.0m, significantly lower than patients with no detected abnormality (median PFS 19.0m) (P 〈 0.05). The median overall survival (OS) of patients with FISH negtive results was 38.0m, significantly higher than those with 13q14, 14q32 or 1q21 abnormality and 17p13/13q14 or more than three abnormalities (P 〈 0.05). Conclusions: This study validates myeloma cells are prone to show complex aberration and FISH is superior in the detection of cytogenetic aberrations to conventional cytogenetics analysis for patients with multiple myeloma. 1q21 had significant correlation to 13q abnormality. 17p13 deletion coexist with 13q14 deletion and 14q32 rearrangeent were used to associate with poor prognosis. 17p13 deletion or 17p13/13q14 deletion was associated with poorer PFS while abnormality of 13q14, 1q21,14q32, 17p13/13q14 or more than 3 abnormalities were correlate with poorer OS. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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  • 7
    In: Biology of Blood and Marrow Transplantation, Elsevier BV, Vol. 17, No. 4 ( 2011-04), p. 542-549
    Type of Medium: Online Resource
    ISSN: 1083-8791
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2011
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    detail.hit.zdb_id: 2057605-5
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  • 8
    In: Carcinogenesis, Oxford University Press (OUP), Vol. 39, No. 11 ( 2018-12-13), p. 1368-1379
    Type of Medium: Online Resource
    ISSN: 0143-3334 , 1460-2180
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
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  • 9
    In: PLoS ONE, Public Library of Science (PLoS), Vol. 9, No. 6 ( 2014-6-11), p. e99174-
    Type of Medium: Online Resource
    ISSN: 1932-6203
    Language: English
    Publisher: Public Library of Science (PLoS)
    Publication Date: 2014
    detail.hit.zdb_id: 2267670-3
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  • 10
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 1990-1990
    Abstract: Bortezomib significantly improved response rates in the treatment of patients with multiple myeloma (MM). However, the process of selecting an optimal bortezomib based regimen as the initial therapy of MM remains ambiguous due to a lack of modern clinical trials demonstrating the efficacy of various bortezomib based treatments. Here, we report four bortezomib-based regimens for treatment of MM patients from three hematological treatment centers in China. Methods Newly diagnosed MM patients in three hematological centers in China between February 1, 2006 and May 31, 2013 were treated with combination therapies including bortezomib plus dexamethasone (PD), or triple combinations of PD with adriamycin (PAD), cyclophosphamide (PCD), and thalidomide (PTD) every 28 days. Results The overall response rate (≥ partial response, ORR) of all the 215 eligible patients was 90.2%. The ORR for PCD, PAD, PTD and PD were 97.4%, 93.2%, 85.3% and 77.8% respectively, while the effects with VGPR or better were 63.7%, 62.7%, 44.2% and 37.8% respectively. The effect of ORR, VGPR and CR/nCR for PCD regimen was significantly better than PD scheme (P = 0.009, 0.011, 0.005 ). The median PFS of all the patients was 29.0 months with significant differences observed between groups (P =0.047). The median OS of all the patients was not reached, but triple combinations of PD with adriamycin (PAD), cyclophosphamide (PCD), and thalidomide (PTD) were more efficient in treatment of MM patients compared to PD (P =0.005). The frequently observed toxicities were neutropenia, thrombocytopenia, fatigue, infection, herpes zoster, and peripheral neuropathy. Incidence of peripheral neuropathy (PN) in PTD group was significantly higher than other three groups, especially grade 2-3 PN. Treatment with anti-viral agent acyclovir significantly reduced the incidence of herpes zoster. Conclusions Our study demonstrated that bortezomib-based regimens were active and well-tolerated in the Chinese MM patients, and triple combinations of PD with adriamycin (PAD), cyclophosphamide (PCD), and thalidomide (PTD) were more efficient for treatment of MM patient, and the patients received PCD or PAD demonstrated significant higher ORR compared to PD. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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